Tightly focused beams of laser light can be used to trap and remotely manipulate polarizable objects. Originally proposed for the trapping of atoms, such devices are also capable of trapping macroscopic, polarizable objects such as latex and glass spheres in the micron size range as well as biological material such as viruses, bacteria, yeast and protozoa, ranging in size from 20 nm to 100 microns. The non-invasive trapping and manipulation of such object have led to the name "optical tweezers" for such devices. The basic principle behind optical tweezers is the gradient force of light which manifests itself when a transparent material with a refractive index greater than the surrounding medium is placed in a light intensity gradient. As light passes through the polarizable object, it induces fluctuating dipoles in the material. These dipoles interact with the electromagnetic field gradient, resulting in a force directed towards the brighter region of the light. Hence the object is pulled into the focus of the laser beam which is the local maximum of the light rigid. Typically, he focus of the laser beam is kept fixed (on the order of the wavelength) so the strength of the trapping force is proportional to the light intensity.
One of the more significant applications of optical tweezers is as a tensiometer. By pulling with the optical tweezers, one can measure the forces associated with certain biomolecular interactions, such as the torsional compliance of bacterial flagella, or the force of single motor molecules like myosin and kinesin. In the later case, the kinesin molecules were attached to micron-sized silica beads with sufficiently sparse surface coverage such that, on average, only one molecule was in contact with a microtubule. Using the silica bead as a handle to pull with the optical tweezers, the force exerted by a single kinesin molecule was observed.
Examples of the devices used in this art and of other relevant work are shown in the following references:
U.S. Pat. No. 4,893,886 to Ashkin et el, Jan. 16, 1990;
U.S. Pat. No. 5,100,627 to Buican et al, Mar.31, 1992; PA1 Molloy, J. E., Burns, I. E., Sparrow, J. C., Tregear, R. T., "Single-Molecule Mechanics of Heavy Meromyosin and Sl Interacting with Rabbit or Drosophila Actins Using Optical Tweezers," Biophysical Journal, Vol, 68, No. 4, 1995, p. 298s; PA1 Nishizawa, T., Miyata, H., Yoshikawa, H., Ishiwata, S., "Mechanical Properties of Single Protein Motor of Muscle Studied by Optical Tweezers," Biophysical Journal, Vol. 68, No. 4, 1995, p. 75s; PA1 Amos, G., Gill, P., "Optical Tweezers," Measurement Science & Technology, Vol. 6, No. 2, 1995, p. 248; PA1 Felgner, H., Mueller, O., Schliwa, M., "Calibration of light forces in optical tweezers," Applied Optics, Vol. 34, No. 6, 1995, p. 977; PA1 Liang, H., Wright, W. H., Rieder, C. L., Salmon, E. D., "Directed Movement of Chromosome Arms and Fragments in Mitotic Newt Lung Cells Using Optical Scissors and Optical Tweezers," Experimental Cell Research, Vol. 213, No. 1, 1994, p. 308. PA1 Wright, W. H., Sonek, G. J., Barns, M. W., "Parametric study of the forces on microspheres held by optical tweezers," Applied Optics, Vol. 33, No. 9, 1994, page 1735; PA1 Wright, W. H., Sonek, G., J., Berns, M. W., "Radiation trapping forces on microspheres with optical tweezers." Applied Physics Letters, Vol. 63, No. 6, 1993, p. 715; PA1 Kuo, S. C., Sheetz, M. P., "Force of Single Kinesin Molecules Measured with Optical Tweezers," Science. Vol. 260, No. 5105, 1993, p. 232; PA1 Block, S. M., "Making light work with optical tweezers," Nature, Vol. 360, No. 6403, 1992, p. 493; PA1 Hong, L, Wright, W. H., Wei, H., Berns, M. W., "Micromanipulation of Mitotic Chromosomes in PTKsub 2 Cells Using Laser-Induced Optical Forces (`Optical Tweezers`)," Experimental Cell Research, Vol. 197, No. 1, 1991, pp. 21-35; PA1 "Atomic fountains; laser tweezers; optical molasses," IEEE Micro., Vol 12, No. 4, 1993, pp. 88-89; PA1 Block, S. M., "15. Optical Tweezes: A New Tool for Biophysics," Modern Cell Biology, Vol. 9, 1990, p. 375; PA1 Dai, J., Sheetz, M.P., "Mechanical properties of neuronal growth cone membranes studied by tether formation with laser optical tweezers." Biophysical Journal, Vol. 68, No. 3, 1995, p. 988; PA1 Afzal, R. S., Treacy. E. B., "Optical tweezers using a diode laser," Review of Scientific instruments, Vol. 63, No. 4, 1993, pp. 2157-2163; PA1 Ashkin, A., "Trapping of atoms by resonance radiation pressure," Physical Review Letters, Vol. 40, 1978, pp. 729-32; PA1 Ashkin, A., Dziedzic, J. M., Bjorkholm, J. E., Chu, S., "Observation of a single-beam gradient force optical trap for dielectric particles," Optics Letters, Vol. 11, 1986, pp. 288-90; PA1 Ashkin, A., Dziedzic, J. M., Yamane, T., "Optical trapping and manipulation of single cells using infrared laser beams," Nature, Vol. 330, 1987, pp. 769-71; PA1 Ashkin, A., Dziedzic, J. M., "Optical trapping and manipulation of viruses and bacteria," Science, Vol. 235, 1987, pp. 1517-20; PA1 Block., S. M., Goldstein, L. S. B., Schnapp, B. J., "Bead movement by single kinesin molecules studied with optical tweezers," Nature, Vol. 348, 1990, pp. 348-52.
Kuo, S.C., Ramanathan, K., Sorg, B., "Single Kinesin Molecules Stressed with Optical Tweezers," Biophysical Journal, Vol. 68, No. 4, 1995, p. 74s;
The disclosures of these references am hereby incorporated by reference in their entirety into this specification.